Vegetable oil-based skin permeation enhancer compositions, and associated methods and systems

Abstract

Methods and compositions are provided which increase the permeability of skin to transdermally administered pharmacologically active agents. The compositions are formulated with one or more vegetable oils as skin permeation enhancers; a preferred composition contains both coconut oil and soybean oil. Drug delivery systems for administering drugs transdermally in combination with the vegetable oil-based enhancer compositions are provided as well.

We claim: 
     
       1. A method for enhancing the flux of a drug through the skin, comprising: applying to the skin of a human patient a composition comprising a pharmaceutically active drug in combination with a permeation enhancing amount of a mixture of vegetable oils selected from the group consisting of almond oil, babassu oil, caster oil, Clark A oil, coconut oil, corn oil, cotton seed oil, jojoba oil, linseed oil, mustard oil, olive oil, palm oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower-seed oil and wheat germ oil, wherein the drug is present in the composition in an amount in the range of from about 1% to about 10% by weight and the mixture of vegetable oils is present in the composition in an amount in the range of from about 5% to about 25% by weight.   
     
     
       2. The method of claim 1, wherein the mixture of vegetable oils is comprised of a mixture of coconut oil and soybean oil. 
     
     
       3. The method of claim 2, wherein the mixture of vegetable oils is present in an amount in the range of from about 5% to about 10% by weight. 
     
     
       4. The method of claim 2, wherein the mixture of vegetable oils comprises 10% to 90% by weight coconut oil and 90% to 10% by weight of soybean oil. 
     
     
       5. The method of claim 1, wherein the drug is administered in combination with an additional permeation enhancer selected from the group consisting of dimethylsulfoxide, dimethylformamide, N,N-dimethylacetamide, declymethylsulfoxide, polyethylene glycol monolaurate, glycerol monolaurate, lecithin, 1-n-dodecylcyclazacycloheptan-2-one, an alcohol, diethylene glycol monoethylether, and diethylene glycol monomethylether. 
     
     
       6. The method of claim 1, wherein the drug is a narcotic analgesic. 
     
     
       7. The method of claim 6, wherein the drug is buprenorphine or a salt thereof. 
     
     
       8. The method of claim 7, wherein the drug is buprenorphine hydrochloride. 
     
     
       9. The method of claim 1, wherein the drug is a calcium channel blocker or an anti-anginal drug. 
     
     
       10. The method of claim 9, wherein the drug is nifedipine. 
     
     
       11. The method of claim 1, wherein the drug is a sedative. 
     
     
       12. The method of claim 11, wherein the drug is triazolam. 
     
     
       13. The method of claim 1, wherein the drug is an antianxiety drug. 
     
     
       14. The method of claim 13, wherein the drug is alprazolam. 
     
     
       15. The method of claim 1, wherein the drug is an antineoplastic agent. 
     
     
       16. The method of claim 15, wherein the drug is tamoxifen. 
     
     
       17. A composition comprising: (a) a therapeutically effective amount of a pharmaceutically active drug; and   (b) a permeation enhancing amount of a mixture of vegetable oils selected from the group consisting of almond oil, babassu oil, castor oil, Clark A oil, coconut oil, corn oil, cotton seed oil, jojoba oil, linseed oil, mustard oil, olive oil, palm oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower-seed oil and wheat germ oil, wherein the drug is present in the composition in any amount in the range of from about 1% to about 10% by weight and the mixture of vegetable oils is present in an amount of about 5% to about 25% by weight.   
     
     
       18. The composition of claim 17, wherein the mixture of vegetable oils is comprised of a mixture of coconut oil and soybean oil. 
     
     
       19. The composition of claim 17, wherein the vegetable oils is present in an amount in the range of from about 5% to about 10% by weight. 
     
     
       20. The composition of claim 18, wherein the mixture of vegetable oils comprises 10% to 90% by weight coconut oil and 90% to 10% by weight of soybean oil. 
     
     
       21. The composition of claim 17, further including an additional permeation enhancer selected from the group consisting of dimethylsulfoxide, dimethylformamide, N,N-dimethylacetamide, declymethylsulfoxide, polyethylene glycol monolaurate, glycerol monolaurate, lecithin, 1-n-dodecylcyclazacycloheptan-2-one, an alcohol, diethylene glycol monoethylether, and diethylene glycol monomethylether. 
     
     
       22. The composition of claim 17, wherein the drug is a narcotic analgesic. 
     
     
       23. The composition of claim 22, wherein the drug is buprenorphine or a salt thereof. 
     
     
       24. The composition of claim 23, wherein the drug is buprenorphine hydrochloride. 
     
     
       25. The composition of claim 17, wherein the drug is a calcium channel blocker or an anti-anginal drug. 
     
     
       26. The composition of claim 25, wherein the drug is nifedipine. 
     
     
       27. The composition of claim 17, wherein the drug is a sedative. 
     
     
       28. The composition of claim 27, wherein the drug is triazolam. 
     
     
       29. The composition of claim 17, wherein the drug is an antianxiety drug. 
     
     
       30. The composition of claim 17, wherein the drug is alprazolam. 
     
     
       31. The composition of claim 17, wherein the drug is an antineoplastic agent. 
     
     
       32. The composition of claim 17, wherein the drug is tamoxifen. 
     
     
       33. A system for the transdermal administration of a drug, comprising: (a) a matrix reservoir comprised of a polymeric material having dispersed therein a pharmaceutically active drug in a therapeutically effective amount and a permeation enhancing amount of a mixture of vegetable oils selected from the group consisting of almond oil, babassu oil, castor oil, Clark A oil, coconut oil, corn oil, cotton seed oil, jojoba oil, linseed oil, mustard oil, olive oil, palm oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower-seed oil and wheat germ oil, wherein the drug is present in the matrix in an amount in the range of about 1% to about 10% by weight and the mixture of vegetable oils is present in the composition in an amount in the range of from about 5% to about 25% by weight;   (b) a backing layer positioned on a surface of the matrix; and   (c) a pressure sensitive adhesive layer positioned on a surface of the matrix opposite the surface having the backing layer thereon.   
     
     
       34. The system of claim 33, wherein the mixture of vegetable oils is comprised of a mixture of coconut oil and soybean oil. 
     
     
       35. The system of claim 34, wherein the mixture of vegetables oils is present in an amount in the range of from about 5% to about 10% by weight. 
     
     
       36. The method of claim 34 wherein the mixture of vegetable oils comprises 10% to 90% by weight coconut oil and 90% to 10% by weight of soybean oil. 
     
     
       37. The system of claim 33, further comprising: an additional permeation enhancer selected from the group consisting of dimethylsulfoxide, dimethylformamide, N,N-dimethylacetamide, declymethylsulfoxide, polyethylene glycol monolaurate, glycerol monolaurate, lecithin, 1-n-dodecylcyclazacycloheptan-2-one, an alcohol, diethylene glycol monoethylether, and diethylene glycol monomethylether.   
     
     
       38. The system of claim 33, wherein the drug is a narcotic analgesic. 
     
     
       39. The system of claim 33, wherein the drug is buprenorphine or a salt thereof. 
     
     
       40. The system of claim 39, wherein the drug is buprenorphine hydrochloride. 
     
     
       41. The system of claim 33, wherein the drug is a calcium channel blocker or an anti-anginal drug. 
     
     
       42. The system of claim 41, wherein the drug is nifedipine. 
     
     
       43. The system of claim 33, wherein the drug is a sedative. 
     
     
       44. The system of claim 43, wherein the drug is triazolam. 
     
     
       45. The system of claim 33, wherein the drug is an antianxiety drug. 
     
     
       46. The system of claim 45, wherein the drug is alprazolam. 
     
     
       47. The system of claim 33, wherein the drug is an antineoplastic agent. 
     
     
       48. The system of claim 47, wherein the drug is tamoxifen.